Quantifying parasite importation in an epidemic-prone zone of northern Kenya

项目摘要 在几个以前流行疟疾的国家，已经消灭疟疾或即将消灭疟疾。疟疾 传播下降后，输入性疟疾对疟疾控制构成越来越大的威胁。人类运动是 输入的主要机制，并可能导致重新引入寄生虫进入生态系统， 疟疾已被消灭，但病媒和宿主仍然存在。这可能会导致重建 传输理论工作预测，来自流行地区的频繁的人员流动可以持续下去， 在疟疾本来会自然消亡的地区传播疟疾。测量实际流行病学 输入性疟疾的影响具有挑战性，但对我们设计或衡量 针对输入性感染的干预措施。在本研究中，我们将直接测量速率和下游 在肯尼亚北方非疟疾流行区图尔卡纳地区，输入性感染的影响。图尔卡纳 以前是易受感染的，但由于以下原因变得越来越容易传播：1）改变 增加病媒丰度的土地使用模式，2）从游牧社区向定居社区过渡，3） 由于石油勘探，进入该地区的人口最近急剧增加， 萃取首先，我们建议通过机场监测来测量寄生虫输入率。在我们 在研究地点，从疟疾流行地区的迁移几乎完全是通过少数每周一次的 商业航班降落在主要城镇洛德瓦尔的一个小机场。通过检查和测试乘客，我们 可以直接测量研究区的输入速率。其次，我们将描述当地的流行病学 通过在研究地区的四个卫生设施建立反应性病例检测，最后我们将 比较输入性感染与本地感染的寄生虫基因型以及基因型多样性 使用高度敏感的深度测序方法。通过确定多样性的数量， 我们可以量化输入对本地传播的影响。虽然条件在 研究区是独特的，在有限的接入点进入该地区，在许多其他方面，他们 反映了发展中世界许多不同地区面临的挑战。增加了人类居住地，改变了土地- 在热带和亚热带地区，使用模式和加强运动是常见的。如果传输被 在我们研究的地区，由于进口的推动，那么它很可能也发生在其他地方， 难以衡量。我们希望我们的研究结果最终能设计出干预措施， 输入性疟疾的威胁，并展示如何衡量这些干预措施的影响， 通过先进的高分辨率基因分型技术最后，图尔卡纳面临的条件不仅是 与疟疾有关。正如最近爆发的登革热、脊髓灰质炎、霍乱和埃博拉病毒所表明的那样， 了解输入与我们日益联系的广泛传染病有关 世界

Project summary Malaria elimination has been achieved or is within reach in several formerly endemic countries. As malaria transmission declines, imported malaria becomes an increasing threat to malaria control. Human movement is the major mechanism of importation and can lead to reintroduction of parasites into an ecosystem where malaria has been eliminated but vectors and hosts are still available. This could lead to re-establishment of transmission. Theoretical work predicts that frequent human circulation from endemic areas can sustain transmission in zones where malaria would otherwise naturally die out. Measuring the actual epidemiologic impact of imported malaria is challenging, but critical to our ability to design or measure the effects of interventions that target imported infections. In this study, we will directly measure the rate and downstream impact of imported infections in the Turkana region, a non-malaria-endemic area of northern Kenya. Turkana was previously epidemic-prone, but has become increasingly vulnerable to transmission due to; 1) changing land-use patterns that increase vector abundance, 2) transition from nomadic to settled communities, and 3) recent and dramatic growth in human circulation into the area as a consequence of oil exploration and extraction. First, we propose to measure the rate of importation of parasites through airport surveillance. In our study site, migration from malaria endemic areas is almost exclusively through the handful of weekly commercial flights into a small airstrip in the main town of Lodwar. By screening and testing passengers, we can directly measure the rate of importation in the study area. Second, we will describe the local epidemiology of malaria by establishing reactive case detection in four health facilities in the study area. Finally, we will compare parasite genotypes, and the diversity of genotypes, in imported versus locally acquired infections using a highly sensitive deep sequencing approach. By identifying the amount of diversity contributed from importation we can quantify the impact of importation on local transmission. Although the conditions in the study area are unique in the limited access points for movement into the region, in many other ways they reflect those facing many different parts of the developing world. Increased human settlement, changing land- use patterns, and enhanced movement are common across the tropics and subtropics. If transmission is being driven by importation in our study area, then it is most likely also happening in other places where it is far more difficult to measure. We expect the results of our study to culminate in the design of interventions to mitigate the threat of imported malaria as well as demonstrate how to measure the impact of these interventions through advanced, high-resolution genotyping techniques. Finally, the conditions facing Turkana are not only relevant to malaria. As recent outbreaks of dengue, polio, cholera, and Ebola have demonstrated, understanding importation is relevant for a broad range of infectious diseases in our increasingly connected world.